Various diacetylenic monomers have long been used as active indicator agents in time-temperature and other ambient condition indicators to indicate the freshness or another characteristic of a host product with which the indicator is associated. Certain diacetylenic monomers undergo a solid-state polymerization reaction changing color, or another visual characteristic, in a predictable and irreversible manner in response to thermal conditions or other stimuli.
Indicators employing a diacetylenic monomer, or a composition of one or more diacetylenic monomers, as an active indicator agent can provide a simple visual indication of the cumulative exposure of a host product to, for example, heat. Such indicators can integrate time and temperature exposure in a predictable, quantitative manner and can be used to monitor the useful shelf life of perishable host products such as a vaccine, a drug or medicament, a foodstuff, an industrial product, or the like. The indicator can provide a color change at a predetermined end point to indicate possible loss of freshness of the host product, or another likely quality of the host product.
To provide a meaningful signal, it is desirable for the response characteristics of the active indicator agent to thermal exposure, or another parameter being measured, to correspond reasonably closely with the response characteristics of the host product with which the indicator is to be associated, over a range of variation of the monitored condition or conditions. Because there is a variety of potential host products for the indicators of the invention, many of which have their own distinctive profiles or patterns of color development responsiveness to thermal exposure and other environmental parameters, it would be desirable to have an extensive catalog of indicator agent response profiles from which a corresponding selection can be made.
Many polymerizable diacetylenic monomer compounds are known or have been suggested. See for example U.S. Pat. Nos. 3,999,946; 4,189,399 and 4,384,980 to Patel and U.S. Pat. Nos. 4,788,151 and 4,789,637 to Preziosi et al. (referenced herein as “Preziosi et al. '151” and “Preziosi et al. '637”, respectively.) A number of the diacetylenic monomers described in these patents, and elsewhere, provide useful color changes upon polymerization in response to environmental conditions to be monitored.
However, only a limited number of known diacetylenic monomers have performance parameters that render them useful for monitoring a perishable or maturing host product and are commercially viable, i.e. can meet a range of criteria for acceptability as a commercial product. This limited number of useful diacetylenic monomers limits the choices available to an indicator formulator seeking a suitable diacetylenic monomer to match with a host product in order to monitor the host product's quality.
One approach to increasing the available choices is to modify the reactivity of a given commercially useful diacetylenic monomer so that it responds differently to a given ambient condition. A single diacetylenic monomer can then provide two or more color development response profiles for matching to host products according to whether the diacetylenic monomer is modified in one or more ways or is unmodified.
As described in Preziosi et al. '151, the activity of an acetylenic compound to environmental stimuli can be altered or controlled by contacting the compound with an effective complexing metal (or metal ion). In a comparable vein, Preziosi et al. '637, describes that the activity can be altered or controlled by contacting the compound with an effective complexing acid.
Also, U.S. Pat. No. 6,924,148 to Prusik et al. (“Prusik '148” herein) discloses varying the reactivity of a diacetylenic monomer by refluxing a solution of the diacetylenic monomer. Both increases and reductions in reactivity are described, depending upon the particular combination of diacetylenic monomer and solvent employed.
Prusik '148 also describes that the refluxed monomer products resulting from refluxing 2,4-hexadiyn-1,6-bis(ethylurea) dissolved in acetic acid for varying times appeared, under microscopic, X-ray diffraction, and other analytical technique observations, to be substantially identical, yet when tested for thermal color-change response they exhibited, with increases in reflux time, increased reactivity.
In addition, U.S. Patent Application Publication No. 2008/0004372 to Prusik et al. discloses use of a reactivity-enhancing adjuvant to adapt the reactivity of a diacetylenic indicator agent to the response characteristics of a host product. Some exemplary adjuvants described include low-temperature polymerization initiators, for example methyl ethyl ketone peroxide, polymerization accelerators, for example cobalt compounds and combinations of initiators and accelerators.
Another approach to providing an indicator agent with a new or modified color-related reactivity profile is to mix two indicator compounds together. Thus, two diacetylenic monomers can be co-crystallized to provide a co-crystallized mixture having a reactivity profile different from either of the starting materials. For example, Miller et al. (Patel) in “Copolymerization of diacetylenes in the crystalline solid state. A method for recording latent fingerprints.”, J. of Applied Polymer Science (1979), 24(3), 883-6, describe the solid state copolymerization of 2,4-hexadiyn-1,6-bis(phenylurethane) and 2,4-hexadiyn-1,6-bis(p-cholorophenylurethane). As described, the presence of oil on a surface on to which a solution of the two compounds is sprayed affects the reactivity of the resultant co-crystallized diacetylenic phase.
Also, “Polymerization in Mixed Crystals”, J. Materials Science, 15 (1980) pages 951-958 to Enkelmann (“Enkelmann 1980” herein) describes that suitably substituted diacetylenes can be co-crystallized to form substitutional solid solutions. Solid state polymerization of mixed crystals of 2,4-hexadiynylene di-p-toluenesulphonate (“1a” in Enkelmann 1980) and up to 20 percent of either 2,4-hexadiynylene di-p-chloro-benzenesulphonate (“1b” in Enkelmann 1980) or di-p-bromobenzene-sulphonate (“1c” in Enkelmann 1980), is described with reference to time conversion curves (pp. 956-958 and FIGS. 9-11). Compound 1a is similar to compound 1b and compound 1c, save that a chlorine atom in the compound 1b and a bromine atom in compound 1c replaces the toluene methyl group in compound 1a.
The active forms of compounds 1b and 1c are described in Enkelmann 1980 as being metastable, and electron diffraction patterns of microcrystals are also described which suggest that these materials are isomorphous with the reactive phase of 1a (page 957). Being “isomorphous” can be understood to mean that their crystal structures are in the same space groups, have the same molecular symmetries, and the same number of molecules in the unit cell.
Stable forms of compounds 1b and 1c, said to be completely unreactive in the solid state and therefore not polymerizable, are described as having triclinic crystal structures that are not isomorphous with the structure of compound 1a. According to Enkelmann 1980, optimum reactivity can be expected when the monomers stack in a distance equal to the polymer repeat unit of 4.9 Å with an angle near 45 degrees (page 954).
Furthermore, “The Solid-State Polymerization, Physical Properties, and Crystal Structures of Diacetylene Mixed Crystals” Makromol. Chem. 184, 1945-1955 (1983) to Enkelmann (“Enkelmann 1983” herein) describes co-crystallization of certain substituted diacetylenes, notably 2,4-hexadiynylene di-p-toluenesulfonate (“1a” in Enkelmann 1983) and 2,4-hexadiynylene di-p-fluorobenzenesulfonate (“1b” in Enkelmann 1983), to form substitutional solid solutions. These compounds differ by only the substitution of methyl groups in the former compound by fluorines in the latter compound. Solid solutions of one diacetylenic monomer in the other at varying concentrations are described. At each concentration the polymerization reactivity of the solid solution was found by Enkelmann to be intermediate between the reactivities of the individual diacetylenics (FIG. 9). Some X-ray diffraction data are also described (pp. 1947-1950).
Neither Enkelmann article appears to describe an indicator agent that would be commercially useful for monitoring the quality of a perishable host product.
Various other co-crystallized mixtures of diacetylenic monomers are also known from patents such as Preziosi et al. '151, Preziosi et al. '637 and Prusik '148, as well as U.S. Pat. Nos. 4,189,399; 4,208,186 and 4,384,980 to Patel, WO 2004/077097 to JP Laboratories and U.S. Pat. No. 7,019,171 to Prusik et al. (“Prusik et al. '171” herein). Some or all of these documents describe co-crystallized mixtures of various hexadiyn bis(alkylurea)s including, in particular, a co-crystallized mixture of 2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(propylurea). The latter co-crystallized diacetylenic monomer mixture has a color development reactivity in response to thermal exposure which is faster than that of either ingredient of the mixture. This indicator agent is useful, inter alia, for monitoring host products having relatively short shelf lives, for example, fresh foodstuffs.
U.S. Pat. No. 4,384,980 to Patel describes a method of preparing an inactive form of diacetylene compounds via slow crystallization of a mixture of two or more diacetylenes from a solvent (column 4, lines 53-68 and column 5, lines 15-17). As described, the inactive forms can be converted to active forms by contact with an activating vapor.
Preziosi et al. '151 describes a procedure for the co-crystallization of various ratios of 2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(propylurea). According to Preziosi et al. '151, X-ray analysis indicated the formation of a solid-solution and NMR (nuclear magnetic resonance, presumably) proton analysis verified the ratios used. A weight ratio of 1:2 parts of 2,4-hexadiyn-1,6-bis (propylurea):2,4-hexadiyn-1,6-bis(ethylurea) is described in Preziosi et al. '151 (Example S) as being the most reactive.
Also, Preziosi et al. '637 describes preparation of a co-crystallized mixture of 2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(butylurea) by precipitation with petroleum ether from a dilute acetic acid solution.
In addition, Prusik '148 discloses refluxing, a mixture of two diacetylenic monomers, 2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(propylurea) in acetic acid to vary the reactivity of the co-crystallized product.
Furthermore, Prusik '171 describes precipitation of polyacetylenic agents with control of a particle size parameter such as mean size or spread. Control is effected by mixing a warm solution of an acetylenic agent with a cold precipitation fluid and appropriate selection of a constituent of the cold precipitation fluid and/or of the temperature conditions. Comparative Example 4 of Prusik '171, which is further described herein, describes recrystallization of a solution in acetic acid of a mixture of 2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(propylurea).
Notwithstanding these and other proposals, it would be desirable to have additional diacetylenic monomer reactivity options available.
The foregoing description of background art may include insights, discoveries, understandings or disclosures, or associations together of disclosures, that were not known to the relevant art prior to the present invention but which were provided by the invention. Some such contributions of the invention may have been specifically pointed out herein, whereas other such contributions of the invention will be apparent from their context. Merely because a document may have been cited here, no admission is made that the field of the document, which may be quite different from that of the invention, is analogous to the field or fields of the present invention.